Gastric adenocarcinomas involving the esophagogastric junction represent a particular therapeutic problem because they lie in the border area between two body cavities: the thorax and the abdomen. The prognosis of gastric adenocarcinomas involving esophagogastric junction is poor because there is widespread lymphatic metastasis, making curative resection difficult. Even in patients with localized disease who are potentially curable, the 5-year survival rate is approximately 20% with curative resection only, somewhat lower than for those with cancer elsewhere in the stomach. The authors conducted a pilot study to evaluate the safety and possible efficacy of adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil (PEF) after curative resection of gastric adenocarcinoma involving esophagogastric junction. Three cycles of adjuvant PEF chemotherapy with cisplatin (20 mg/m2/day intravenously on days 1-5), etoposide (100 mg/m2/day intravenously on days 1, 3, and 5), and 5-fluorouracil (800 mg/m2/day continuous intravenous infusion on days 1-5) were given every 3 weeks after curative resection of gastric adenocarcinoma involving the esophagogastric junction. Between November 1989 and June 1995, a total of 50 patients with postoperative stage II, IIIA, or IIIB disease entered this trial. In 14 of 50 patients (28%), the disease recurred during the follow-up of 4-83 months (median 26 months). Disease-free survival was 4-83+ months (median 48 months), and the actuarial 5-year disease-free survival rate was 48% (95% CI: 41% to 55%). Overall survival was 4-83+ months (median 62 months), and the actuarial 5-year survival rate was 54% (95% CI: 40% to 68%). The prognostic factor analysis showed that the postoperative N stage and the interval between surgery and chemotherapy affected disease-free survival and overall survival. The toxicities of PEF adjuvant chemotherapy were leukopenia, nausea/vomiting, and alopecia, but they were mostly mild and reversible except in one patient who died because of treatment-related sepsis. Adjuvant chemotherapy with three cycles of PEF regimen was well tolerated and seems to be a promising treatment for gastric adenocarcinoma involving the esophagopstric junction, in comparison with previous treatments. To define the efficacy of adjuvant PEF chemotherapy for gastric adenocarcinoma involving esophagogastric junction, prospective randomized trials are warranted.